<scp>cGAS</scp>
            facilitates sensing of extracellular cyclic dinucleotides to activate innate immunity

Liu, Haipeng; Moura-Alves, Pedro; Pei, Gang; Mollenkopf, Hans-Joachim; Hurwitz, Robert; Wu, Xiangyang; Wang, Fei; Liu, Siyu; Ma, Mingtong; Fei, Yiyan; Zhu, Chenggang; Koehler, Anne-Britta; Oberbeck-Mueller, Dagmar; Hahnke, Karin; Klemm, Marion; Guhlich-Bornhof, Ute; Ge, Baoxue; Tuukkanen, Anne; Kolbe, Michael; Dorhoi, Anca; Kaufmann, Stefan H. E.

doi:10.15252/embr.201846293

Cited by 56 publications

(54 citation statements)

References 61 publications

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“…Notably, ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP-1) can degrade extracellular cGAMP (61) ( Figure 2B). Besides triggering STING, these exogenous cGAMP can directly bind to cGAS and prompt its activation as well (62). After binding to cGAMP, the "lid" region of the STING dimer undergoes a conformational change that converts STING from an inactive "open" formation to an active "closed" formation.…”

Section: Cgamp Can Transfer Between Cells and Activate Stingmentioning

confidence: 99%

Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response

2020

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Double-stranded DNA (dsDNA) sensor cyclic-GMP-AMP synthase (cGAS) along with the downstream stimulator of interferon genes (STING) acting as essential immunesurveillance mediators have become hot topics of research. The intrinsic function of the cGAS-STING pathway facilitates type-I interferon (IFN) inflammatory signaling responses and other cellular processes such as autophagy, cell survival, senescence. cGAS-STING pathway interplays with other innate immune pathways, by which it participates in regulating infection, inflammatory disease, and cancer. The therapeutic approaches targeting this pathway show promise for future translation into clinical applications. Here, we present a review of the important previous works and recent advances regarding the cGAS-STING pathway, and provide a comprehensive understanding of the modulatory pattern of the cGAS-STING pathway under multifarious pathologic states.

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Section: Cgamp Can Transfer Between Cells and Activate Stingmentioning

confidence: 99%

Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response

2020

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“…The CDNs are significant second messenger molecules in various organisms, including eukaryotes and prokaryotes. Cytosolic CDNs are sensed by STING and prime host cells by activating innate immune responses via IFN 119. Likewise, extracellular microbes and dying cells can discharge CDNs.…”

Section: Regulation Of Innate Immune Responsesmentioning

confidence: 99%

“…Numerous bacteria yield CDNs, for example, cyclic di‐AMP or cyclic di‐GMP, as signaling particles. When CDNs interact with the cytosol, they are recognized by STING, which prompts the induction of IFN‐β and various cytokines and chemokines 119. CDN interaction with STING incites its relocation from the ER to produce perinuclear punctate assemblies.…”

Section: Regulation Of Innate Immune Responsesmentioning

confidence: 99%

“…Assimilated CDNs openly interact with cGAS, prompting the resultant dimerization, and the establishment of a cGAS‐STING assembly that might initiate downstream signaling. The immune responses to extracellular CDNs are expected at ten‐ to 100‐fold higher concentrations of CDN than those utilized for direct transport into the cytosol by digitonin‐interceded membrane permeabilization, which might suggest why an innate immune response to extracellular CDNs has not been witnessed earlier 119. Similarly, cGAS encourages the recognition of CDNs trafficked intracellularly through endocytosis, perinuclear amassing, and consequent STING‐mediated induction of IFN.…”

Section: Regulation Of Innate Immune Responsesmentioning

confidence: 99%

“…Similarly, cGAS encourages the recognition of CDNs trafficked intracellularly through endocytosis, perinuclear amassing, and consequent STING‐mediated induction of IFN. Therefore, eCDNs include bacterial and damage‐associated molecular patterns (DAMPs) that add to host‐associated microbial crosstalk during health and disease 119…”

Section: Regulation Of Innate Immune Responsesmentioning

confidence: 99%

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Regulation of cGAS‐Mediated Immune Responses and Immunotherapy

et al. 2020

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Early detection of infectious nucleic acids released from invading pathogens by the innate immune system is critical for immune defense. Detection of these nucleic acids by host immune sensors and regulation of DNA sensing pathways have been significant interests in the past years. Here, current understandings of evolutionarily conserved DNA sensing cyclic GMP‐AMP (cGAMP) synthase (cGAS) are highlighted. Precise activation and tight regulation of cGAS are vital in appropriate innate immune responses, senescence, tumorigenesis and immunotherapy, and autoimmunity. Hence, substantial insights into cytosolic DNA sensing and immunotherapy of indispensable cytosolic sensors have been detailed to extend limited knowledge available thus far. This Review offers a critical, in‐depth understanding of cGAS regulation, cytosolic DNA sensing, and currently established therapeutic approaches of essential cytosolic immune agents for improved human health.

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Regulation of Type I Interferon and Autophagy in Immunity against Mycobacterium Tuberculosis: Role of CGAS and STING1

Malik,

Shariq,

Sheikh

et al. 2024

Advanced Biology

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Mycobacterium tuberculosis (M. tb) is a significant intracellular pathogen responsible for numerous infectious disease‐related deaths worldwide. It uses ESX‐1 T7SS to damage phagosomes and to enter the cytosol of host cells after phagocytosis. During infection, M. tb and host mitochondria release dsDNA, which activates the CGAS‐STING1 pathway. This pathway leads to the production of type I interferons and proinflammatory cytokines and activates autophagy, which targets and degrades bacteria within autophagosomes. However, the role of type I IFNs in immunity against M. tb is controversial. While previous research has suggested a protective role, recent findings from cgas‐sting1 knockout mouse studies have contradicted this. Additionally, a study using knockout mice and non‐human primate models uncovered a new mechanism by which neutrophils recruited to lung infections form neutrophil extracellular traps. Activating plasmacytoid dendritic cells causes them to produce type I IFNs, which interfere with the function of interstitial macrophages and increase the likelihood of tuberculosis. Notably, M. tb uses its virulence proteins to disrupt the CGAS‐STING1 signaling pathway leading to enhanced pathogenesis. Investigating the CGAS‐STING1 pathway can help develop new ways to fight tuberculosis.

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cGAS facilitates sensing of extracellular cyclic dinucleotides to activate innate immunity

Cited by 56 publications

References 61 publications

Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response

Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response

Regulation of cGAS‐Mediated Immune Responses and Immunotherapy

Regulation of Type I Interferon and Autophagy in Immunity against Mycobacterium Tuberculosis: Role of CGAS and STING1

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